title: Efficacy of verapamil as an adjunctive treatment in children with drug-resistant epilepsy: a pilot study.
abstract: OBJECTIVE
  Verapamil, a voltage-gated calcium channel blocker, has been occasionally reported to have some effect on reducing seizure frequency in drug-resistant epilepsy or status epilepticus. We aimed to investigate the efficacy of verapamil as add-on treatment in children with drug-resistant epilepsy.
  
  
  METHODS
  Seven children with drug-resistant structural-metabolic, unknown or genetic (e.g., Dravet syndrome [DS]) epilepsy received verapamil as an add-on drug to baseline antiepileptic therapy. Verapamil was slowly introduced at the dosage of 1mg/kg/day and titrated up to 1.5mg/kg/day. After completing the titration period, patients entered a 14-month maintenance period and were followed up at 3, 8, and 14 months. Heart monitoring was performed at baseline and at each follow-up. The primary outcome measure was the response of seizures to verapamil.
  
  
  RESULTS
  Three subjects with genetically determined DS showed a partial (reduction of 50-99%) response for all types of seizures. A patient with DS without known mutation showed a partial control of all types of seizures in the first 13 months; then seizures worsened and verapamil was suspended. Two patients with structural epilepsy and one with Lennox-Gastaut syndrome showed no improvement. Any side effects were recorded.
  
  
  CONCLUSIONS
  Add-on treatment with verapamil seems to have some effect in controlling seizures in patients with genetically determined DS. Our observations justify further research on the relationship between calcium channels, calcium channel blockers, and channelopathies.
authors.affiliation: Child Neurology Division, Department of Pediatrics, Umberto I Hospital, Sapienza University of Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nicita
authors.affiliation: Child Neurology Division, Department of Pediatrics, Umberto I Hospital, Sapienza University of Rome, Italy. Electronic address: childneurology.sapienzaroma@live.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Spalice
authors.affiliation: Child Neurology Division, Department of Pediatrics, Umberto I Hospital, Sapienza University of Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Papetti
authors.affiliation: Children Department, Danish Epilepsy Centre, Dianalund, Denmark.
authors.forename: Marina
authors.initials: M
authors.lastname: Nikanorova
authors.affiliation: Child Neurology Division, Department of Pediatrics, Umberto I Hospital, Sapienza University of Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Iannetti
authors.affiliation: NESMOS Department, Chair of Pediatrics, Child Neurology, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Parisi
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000187:drug effects / Q000502:physiology*; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010865:Pilot Projects; D016896:Treatment Outcome; D014700:Verapamil / Q000008:administration & dosage*
chemical_list: D000927:Anticonvulsants; D014700:Verapamil
keywords: Blood–brain barrier; Dravet syndrome; Drug-resistance; Epilepsy; Multidrug transporters; P-glycoprotein; SCN1A; SMEI; Verapamil